ASCO: Jakavi Effective in Blood Cancer

CHICAGO -- A drug approved to treat one member of a group of blood cancers is also effective in another, a researcher said here.

by Michael Smith Michael Smith North American Correspondent, MedPage Today
June 05, 2014

Action Points

Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.

Note that this randomized trial demonstrated that the JAK inhibitor ruxolitinib significantly reduced hematocrit and spleen size in patients with polycythemia vera.

Be aware that long-term data on progression and adverse event rates are not yet available.

CHICAGO -- A drug approved to treat one member of a group of blood cancers is also effective in another, a researcher said here.

In a phase III randomized controlled trial, ruxolitinib (Jakavi) improved several of the symptoms of polycythemia vera (PV), an incurable myeloproliferative neoplasm, according to Srdan Verstovsek, MD, PhD, of MD Anderson Cancer Center in Houston.

In patients resistant to or intolerant of hydroxyurea, the standard treatment, the drug significantly improved hematocrit control without the need for phlebotomy and reduced spleen size -- two key treatment goals, Verstovsek reported at the annual meeting of the American Society of Clinical Oncology.

PV is characterized by increased production of red blood cells, disease-related symptoms such as pruritus, and an increased risk of vascular events such as thrombosis and hemorrhage, he noted.

Importantly, it is also characterized by the JAK/STAT signaling pathway, which is inhibited by the tyrosine kinase ruxolitinib. The drug was approved in 2011 to treat myelofibrosis, another myeloproliferative neoplasm that involves the JAK1 and JAK2 enzymes.

In the so-called RESPONSE trial, Verstovsek and colleagues tested the idea that the drug would also work in PV -- randomizing 222 patients to get the drug or best available other treatment for 80 weeks.

The primary endpoint was a composite -- a normal hematocrit level, defined as below 45, and a reduction in spleen size by at least 35% by week 32 of treatment.

At week 32, patients in the control arm were permitted to cross over to the ruxolitinib arm and all but a handful did so, Verstovsek said.

But at that point, he reported:

21% of the ruxolitinib patients had reached the composite endpoint, compared with 1% of those on best available treatment. The proportions yielded an odds ratio of 28.64 in favor of the drug, which was significant at P<0.0001.

60% of ruxolitinib patients reached the hematocrit endpoint, compared with 20% on best available treatment.

38% reached the spleen reduction goal, compared with 1% of those in the control arm.

As well, 23.6% of ruxolitinib patients reached a complete hematologic response, compared with 8.9% of control patients, a difference that was significant at P=0.003.

The drug also improved the total symptom score, as well as individual symptom clusters, he said, and with a median follow-up of 81 weeks, 85% of patients originally randomized to the drug were still taking it.

The main strength of the study was that it met a "well-conceived endpoint," commented Guido Marcucci, MD, of Ohio State University Comprehensive Cancer Center in Columbus, in a formal discussion after the presentation.

It also met all of its secondary endpoints and showed that the drug had a "relatively favorable" safety profile, he said.

The main weakness, on the other hand, is that almost all of the control patients crossed over to the ruxolitinib arm as soon as they were able, Marcucci said.

"We don't have data yet on those patients," he said, and it would be interesting to know if they have the same favorable response.

He also noted that there is no pharmacodynamic data, which is "important because we want to know why only 21% and no more had a response."

Marcucci added that the study shows the drug improves the symptoms of the disease, but it remains an open question whether it changes the natural history of the disease.

The answer, he said, is "probably not ... which underlines that we know relatively little" about the biology of the disease.

The study was supported by Novartis. Verstovsek disclosed relationships with Incyte. Employees of both companies were among the authors.

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